Chronic Kidney Disease (CKD) Platelet Study

Phase 3

Completed

Conditions: Heart Attack
Chronic Kidney Diseases
Stroke, Ischemic

Interventions: Drug: Ticagrelor 90mg
Drug: Clopidogrel 75mg
Drug: Aspirin 81 mg

Registration Number: NCT03649711

Lead Sponsor: University of Arkansas

Brief Summary: This study evaluates how aspirin, clopidogrel and ticagrelor work in people with chronic kidney disease (CKD) compared to people with normal kidneys. In the first part of the study, half of CKD participants will be randomly assigned to ticagrelor and aspirin, while the other half will be assigned to clopidogrel and aspirin in a blinded fashion. The treatment duration will be two weeks. After recruiting CKD participants the investigator will recruit controls with normal kidney function that will receive only ticagrelor and aspirin for two weeks.

Detailed Description: It is known that people with chronic kidney disease (CKD) are at higher risk to have heart and blood vessel problems like heart attack and stroke compared to people that do not have kidney problems. Aspirin, clopidogrel and ticagrelor prevent blood clots building up in the vessels. If a blood clot is present in one vessel, it could stop oxygen carrying blood to get to a specific organ, and that could cause problems like heart attack or stroke. There is very little knowledge about the way this group of medicines works in people with chronic kidney disease as well as it works in individuals with normal kidney function.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 76

Inclusion Criteria

Males and females, aged 18-91 years
Ability to understand and sign informed consent after the nature of the study has been fully explained
CKD participants: Non-dialysis CKD patients: Presence of CKD with an estimated GFR of <30 mL/min/1.73 m2 for a period of ≥3 months, as defined by the National Kidney Foundation (NKF) and determined with the CKD-EPI creatinine-based formula
Controls with normal kidney function: participants with an estimated GFR >90 mL/min/1.73 m2 as determined by the CKD-EPI creatinine-based formula and a urine albumin-to-creatinine ratio <30 mg/g as defined by the National Kidney Foundation

Exclusion Criteria

No healthcare power of attorney to sign informed consent
Unwillingness or inability to participate in the protocol or comply with any of its components.
Subjects unable or unwilling to stop taking:
- Aspirin and other antithrombotic agents, like cilostazol, ranolazine, aggrenox, prasugrel, warfarin, xarelto, pradaxa, eliquis.
- Glycoprotein IIb/IIIa antagonist (abciximab-ReoPro, eptifibatide-Integrilin, tirofiban-Aggrastal)
- NSAIDs and PPIs
- Fish oil, Vitamin E and herbal supplements
Acute kidney injury superimposed on CKD
Kidney transplant or any other solid organ transplant recipient
End-stage kidney disease on maintenance dialysis (peritoneal or hemodialysis)
Nephrotic syndrome defined as nephrotic range proteinuria, hypoalbuminemia, hyperlipidemia and generalized edema
Recent hospitalization or surgery <3 months
Acute coronary or cerebrovascular event in the last 12 months
Blood dyscrasias, active bleeding, or bleeding diathesis
Gastrointestinal bleeding in the last 6 months
Recent treatment (<30 days) with a glycoprotein IIb/IIIa antagonist (Integrelin).
Hematocrit <25%, white blood cell count >20,000/μL, or platelet count <50,000/μL
Any active malignancy or liver disease.
Pregnancy
Positive urine pregnancy test in a woman of childbearing potential prior to study entry. A female of childbearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Patients must not be nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CKD-Ticagrelor	Aspirin 81 mg	Ticagrelor 90 mg twice daily (double blind, random assignment) + aspirin 81 mg/d
CKD-Clopidogrel	Aspirin 81 mg	Clopidogrel 75 mg/day in the morning and a matching placebo in the evening to conceal frequency (double blind, random assignment) + aspirin 81 mg/d
Control-ticagrelor	Ticagrelor 90mg	Open label ticagrelor, 90 mg twice daily + aspirin 81 mg/d
CKD-Ticagrelor	Ticagrelor 90mg	Ticagrelor 90 mg twice daily (double blind, random assignment) + aspirin 81 mg/d
CKD-Clopidogrel	Clopidogrel 75mg	Clopidogrel 75 mg/day in the morning and a matching placebo in the evening to conceal frequency (double blind, random assignment) + aspirin 81 mg/d
Control-ticagrelor	Aspirin 81 mg	Open label ticagrelor, 90 mg twice daily + aspirin 81 mg/d

Primary Outcome Measures

Name	Time	Method
ADP Induced Platelet Aggregation	2 weeks	We will use summary statistics to describe the distribution of the data. Post-treatment ADP-induced WBPA value in ohms (Ω) will be the primary outcome variable. We will use an analysis of covariance (ANCOVA) model to compare the treatment effects of ticagrelor vs. clopidogrel in CKD patients because this approach has higher statistical power than other methods to analyze drug effects. T

Secondary Outcome Measures

Name	Time	Method
Platelet Surface P-selectin Expression	2 weeks	Platelet surface P-selectin expression was measured using flow cytometry before and after treatment.

Trial Locations

Locations (2): Central Arkansas Veterans Affairs Hospital
🇺🇸
Little Rock, Arkansas, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States